High yielding synthesis of heterocyclic β-substituted alanine derivatives

Abstract

Heterocyclic β-substituted alanine derivatives such as β-(pyrazol-1-yl) and β-(1,2,4-triazol-1yl)-alanine are synthesized in high yields by a Michael addition of heterocyclic nucleophiles to N,N-bis(tert-butyloxycarbonyl)dehydroalanine methyl ester, using mild reaction conditions and simple work-up procedures.

Gold‐Catalyzed C‐3‐Alkylation of 7‐Azaindoles Through Michael‐Type Addition to α,β‐Enones

“…The conjugate addition of azaindoles to electron-deficient olefins to give N-1-alkylated derivatives has previously [73] been reported to occur under basic conditions and the formation of Michael adducts involved the N-alkylation of anionic 7-azaindoles obtained from 1 by the addition of a base such as K 2 CO 3 in an aprotic solvent.…”

Synthesis of alkyl 2-benzoylamino-3-(4,5-dicyano-1H-imidazol-1-yl)propenoates

“…Among them are (1H-imidazol-1-yl)-substituted amino acid derivatives. For example, 2-amino-3-(1H-imidazol-1-yl)propanoic acid and its derivatives have been prepared by the ring-opening reaction of serine β-lactone derivatives with 1-(trimethylsilyl)imidazole 1 or imidazole, 2 or by conjugate addition of imidazole to didehydroalanine derivatives, [3][4][5][6] and has been used in studies concerning the design of orally active renine inhibitors. 2 This amino acid has also been synthesized by the condensation of diethyl α-acetamido-α-(dimethylaminomethyl)malonate methiodide with sodium imidazole in liquid ammonia; and the biological activity concerning the ability to support the growth of a histidine-requiring bacterial mutant has been examined.…”

Enzymatic resolution for the preparation of enantiomerically enriched D‐β‐heterocyclic alanine derivatives using Escherichia coli aromatic L‐amino acid transaminase

“…Unnatural amino acids which show rare and special pharmacological effects and low degradation rates in living organism are drawing great attention as they become im-portant chiral building blocks for the synthesis of various pharmaceuticals (Bommarius et al, 1998;Fotheringham et al, 1997;Taylor et al, 1998). As an example of the unnatural amino acids, h-heterocyclic alanine derivatives such as pyrazolylalanine, triazolylalanine, and imidazolylalanine are known as important drugs for treatment of diabetes (Ferreira et al, 1999;Ikegami and Murakoshi, 1994;Rolland-Fulcrand et al, 2000). Several attempts for the synthesis of h-heterocyclic alanine derivatives have been described (Arnold et al, 1988;Barbaste et al, 1998;Farthing et al, 1996;Ferreira et al, 1999;Rolland-Fulcrand et al, 2000).…”